The purpose of the proposed research is to determine the metabolic and hemodynamic concomitants of irreversible cerebral ischemia in man. The broad goals of the project are to characterize the local pathophysiological changes brought about by cerebral ischemia and to relate these data to the clinical findings and outcome, and later to the treatment of this disorder. The study protocol will generate data concerning: the neurological status, prognosis, X-ray and NMR CT, neuropsychological function, and the cerebral consumption of glucose and oxygen along with cerebral blood flow using positron emission tomography (PET) in human subjects. Patients suffering cerebral ischemia as well as normal elderly controls will be included in the study. Serial measurements will be made over time during the acute, recovery, and chronic phases of cerebral ischemia. These data will be analyzed with the aid of a computer-based data management system and computer-aided image processing. The specific aims of the project are: 1) to determine whether or not critical levels of metabolism and blood flow exist which distinguish tissue which is reversibly affected from that which is irreversibly damaged by ischemia, 2) to determine whether or not penumbras of inhomogeneities in flow and metabolism exist in tissue surrounding the core of an infarction, 3) to explore the impact of focal cerebral lesions on the function of interrelated butnonischemic brain regions (diaschisis), 4) to assess the effect of normal aging on cerebral metabolism and blood flow, and 5) to determine what effects, if any, tissue ischemia and aging have on the operational models currently used in the study of cerebral metabolism. Current methods using PET yield the most complete picture yet available of the in vivo workings of the human brain. Application of this method to clinical studies could help to resolve uncertainties concerning the pathophysiology of cerebral ischemia and its treatment. Metabolic data may provide a reliable benchmark with which to describe the natural history of cerebral ischemia and thus to assess the impact of various therapeutic interventions. It can be expected that other markers of neural function will be made available in the future. Pivotal to the success of this work is the ability to work effectively in both the technical and clinical milieu. Achieving investigative proficiency in these differing spheres is a stated long-term goal.